NOCOSMIC — Result In Brief

Non-coding mutations in cancer

European researchers investigated how mutations in the non-coding part of the genome could trigger cancer development. Their results unveil a novel perspective in cancer genetics with potential clinical implications.

Up to now the consensus is that most types of cancer emerge from mutations in certain genes that lead to aberrant expression or novel products. As less than 2 % of the human genome is protein-coding, it is very likely that non-coding mutations exist and possibly disrupt transcription factor-binding sites or functions of non-coding RNAs. Overall, the consequences of mutations in non-coding regions of the genome are not well understood. Currently, there are no methods available for the prioritisation of somatic non-coding variants in tumour genomes.

The primary objective of the EU-funded NOCOSMIC (Prioritization of non-coding somatic mutations in cancer) project was to understand the role of non-coding mutations in cancer. Towards this goal, scientists designed a method that analysed 50bp sequences spanning the entire human genome to identify frequently mutated regions.

Application of this method to over 1 300 cancer genomes enabled the identification of both coding and non-coding regions that are recurrent targets of somatic mutations in cancer. Apart from novel recurrently mutated regions, researchers discovered tumour driver mutations in regions with high evolutionary conservation.

Overall, the findings of the NOCOSMIC study underscored the importance of non-coding recurrent mutations in cancer development. This has significant ramifications for cancer research as it explains the aberrant expression of non-coding RNAs in cancer cells and illustrates the importance of regulatory regions. In the future, scientists need to design drugs or interventions that target the entire cancer genome.